Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung.
Chemoprevention of genome, transcriptome, and proteome alterations induced by cigarette smoke in rat lung.
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DOI：
10.1016/j.ejca.2005.04.011
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发表时间：
2005-09
影响因子：
8.4
通讯作者：
A. Izzotti;M. Bagnasco;C. Cartiglia;M. Longobardi;R. Balansky;A. Merello;R. Lubet;S. De Flora
中科院分区：
文献类型：
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作者：
A. Izzotti;M. Bagnasco;C. Cartiglia;M. Longobardi;R. Balansky;A. Merello;R. Lubet;S. De Flora
后基因组方法学为评估癌症化学预防药物的安全性和有效性提供了新的工具。我们将大鼠暴露在环境香烟烟雾(ECS)中28天，同时口服或不口服N-乙酰半胱氨酸(NAC)。32P标记后评估，ECS导致DNA加合物水平增加10倍，而NAC显著降低该水平。在抗体芯片检测的518个蛋白质中，ECS刺激了56个涉及应激反应、蛋白质去除、细胞复制、凋亡、吞噬和免疫反应的活动。NAC单独作用不改变任何蛋白质的含量，而显著减少ECS诱导的6种蛋白质的数量。基因芯片检测到278个相关基因的表达强度与蛋白质含量显著相关。这些观察到的可被NAC减弱的分子变化，部分代表了适应性反应，部分反映了与吸烟相关的疾病的发病机制，包括肺癌、哮喘、慢性支气管炎和肺气肿。
Postgenomic methodologies have provided novel tools for evaluating safety and efficacy of cancer chemopreventive agents. We exposed rats to environmental cigarette smoke (ECS) for 28 days, with or without oral administration of N-acetylcysteine (NAC). As assessed by32P-postlabelling, ECS caused a 10-fold increase of DNA adduct levels, which were significantly reduced by NAC. Of 518 proteins tested by antibody microarray, ECS stimulated 56 activities involved in stress response, protein removal, cell replication, apoptosis, phagocytosis, and immune response. NAC alone did not change the amounts of any protein, whereas it significantly decreased the amounts of 6 ECS-induced proteins. The intensity of expression of 278 related genes, assessed by cDNA microarray, was significantly correlated with protein amounts. These observed molecular alterations, which can be attenuated by NAC, represent in part adaptive responses and in part reflect mechanisms contributing to the pathogenesis of smoke-related diseases, including lung cancer, asthma, chronic bronchitis, and emphysema.